Non-melanoma skin cancers (NMSCs) i.e. cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are the most common malignancies in organ transplant recipients (OTRs). OTRs have a 65-250x greater risk of cutaneous SCCs and a 10x increased risk of BCCs than the general population, and when they do occur, NMSCs behave more aggressively. For example, the rate of SCC metastases in OTRs is 7%, which is much higher than the general population. Current methods for prevention of NMSCs consist primarily of sun and tanning bed avoidance and the regular use of sunscreens. These measures have proven to be inadequate. Oral retinoids are effective chemopreventive agents in OTRs, but at the doses required, are poorly tolerated. UAB30 is a novel RXR selective retinoid (i.e. rexinoid), which is a potent chemopreventive agent for SCCs and other epithelial tumors in animal models, and has been shown to be well-tolerated in phase I human clinical trials in normal individuals. We plan to conduct a randomized, double-blind, placebo-controlled biomarker study of oral UAB30 in OTRs with actinic damage and a history of BCC and/or SCC. The purpose of this short-term clinical trial is to determine whether UAB30 has a protective effect on molecules associated with the development of NMSC in OTRs. We plan to determine whether a greater percentage of OTRs randomized to receive oral UAB30 will have >30% reduction in skin biomarkers associated with development of NMSC. Cyclin D1, a marker of cell proliferation, will be the primary endpoint. Other biomarkers to be evaluated include additional molecules associated with proliferation and apoptosis, off target molecules in the DNA damage repair and Src pathways, all-trans-retinoic acid genes, and parameters associated with the host anti-tumor immune response. We also plan to investigate whether premalignant actinic keratoses will undergo regression and if the onset of new actinic keratoses will be inhibited in OTR and non-OTR participants randomized to UAB30. Finally, we will evaluate the safety of oral UAB30 in OTRs. This is a rational first step to determine the feasibility of testing UAB30 as a chemopreventive agent for NMSC in OTRs prior to a larger, long-term, and more costly clinical trial. It may also identify procedures for screening future rexinoids for their chemopreventive actions in vivo in humans.